Adherence to clinical care and adherence to antiretroviral medications (ARV) are critical factors to effectively treat HIV disease, improve health outcomes in HIV positive patients, and can also reduce infectivity, transmission, and the development of resistance. These two types of adherence (collectively referred to as treatment adherence) are facilitated and hindered by diverse factors that represent an interplay between internal and external factors. For this reason, interventions to improve treatment adherence must attend to and impact multiple factors. The Deep South HIV-positive population has particular need for effective interventions to maximize treatment adherence because of the region's well-documented high prevalence of HIV, as well as its history of poor health outcomes in HIV disease as well as other disease conditions. The current study seeks to develop and provide initial evaluations of a theory-based treatment adherence intervention to be delivered in concert with regularly scheduled clinical care with three specific aims: 1) To identify the important Information, Motivation, and Behavioral Skills (IMB) factors related to treatment adherence for this Deep South population, in relation to personal and contextual variables including structural barriers, substance abuse, and mental health problems including depression, denial, and stigma;2) To adapt and standardize the theory-based intervention to address the identified IMB factors, and to address the contextual variables through case management and clinical care systems;3) To pilot test this intervention in a randomly controlled trial for improving medication adherence in those with a pre-existing medication adherence problem, and for improving adherence to clinical care in those with a history of gaps in care. Treatment adherence will be examined for between-group differences over time and for dose response to the intervention. Results from the present study will inform a Phase III trial of the developed and refined treatment adherence intervention. Inadequate adherence to prescribed antiretroviral medication has clear deleterious effects, both to the individual HIV positive patient's health outcomes and in terms of the epidemiology of resistant virus. Despite the increasing attention devoted to adherence intervention development, few projects have targeted adherence support in the Deep South, where the prevalence of HIV is higher than any other region of the US. In this region where acute limitations in resources characterize both patients and clinical care facilities alike, interventions that target and support adherence to both ARV medication regimens and attendance to clinical care appointments that are yoked to existing services and emphasize real-world feasibility are critical. The current project seeks to develop and provide initial evaluations of a theory-based adherence support intervention for a clinic population of HIV positive patients on ARVs in the Deep South. By using well-developed theories of health behavior change, the intervention will target improvements in ARV adherence and clinical care utilization in a manner that emphasizes translation and feasibility of uptake in terms of utilization of existing systems of care with minimal additional resource commitment requirements. This research will also uniquely advance theory-building in the area of case-manager delivered IMB-based interventions for ARV adherence and maintenance in clinical care in the context of multiple structural and personal barriers.